The VRC's highest priority remains development of a vaccine or other immune modulator that prevents HIV acquisition. The overarching objectives of this task include activities to produce HIV candidate vaccines or broadly neutralizing antibodies for passive prevention trials and to develop novel product development technologies to enable faster timelines to clinical trial for HIV vaccine candidates. OBJECTIVE 1: HIV VACCINE DEVELOPMENT BACKGROUND No vaccine is currently available to prevent HIV infection. The moderate protection afforded in one vaccine efficacy trial was associated with the induction of antibodies to the V1V2 region of HIV envelope. A stabilized soluble HIV env trimer is antigenically preferable to current uncleaved trimers and should serve as an improved immunogen to stimulate antibodies to the major neutralization epitopes, including V1V2 antibodies. Thus, the ability to manufacture a stabilized trimer will advance the development of HIV vaccines, used alone or in combination with existing vaccine platforms, by accelerating clinical testing of multiple vaccine strategies that are currently stalled for lack of an appropriate HIV env immunogen. PROJECT REQUIREMENTS Despite the development and structural determination of a soluble trimer of HIV Env gp140 (BGSOS SOSIP664) difficulties in manufacturability and stability hamper its clinical development. Using data from new atomic level crystal structures, the VRC has determined a method for creating a gp140 trimer with improved stability and manufacturability. This trimer binds all classes of broadly neutralizing antibodies, but not non-neutralizing antibodies. In addition, we have determined optimal sequence characteristics for the potential to elicit VlV2 antibodies. 1/ The VRC requests cGMP manufacturing and technology transfer* support for a recombinant stabilized gp140 trimer vaccine candidate for the VRC to advance to clinical trials. OBJECTIVE 2: HIV MPER BNABS FOR PREVENTION, THERAPY, OR CURE BACKGROUND Production and clinical testing of long half-life bNAbs targeting multiple neutralizing epitopes will improve the coverage and likely success of bNAbs for prophylaxis, therapy, and cure strategies. Advances in this area will broadly impact strategies for: 1) prevention of transmission from HIV-1 infected mothers to newborn and breastfeeding infants; 2) prevention of HIV infection by sexual transmission; and 3) therapeutic application in HIV-1 infected individuals (including elimination of the latent reservoir). PROJECT REQUIREMENTS 1/ The VRC requests cGMP manufacturing and technology transfer support for 1st generation MPER bNAb candidates for the VRC to advance to clinical trials. *All process development activity will be independently undertaken by the VRC. However, general technology transfer activities, involving potential process transfer to the VCMP, are included in the request for support.